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Calanolide A

Scientific Name(s): Calophyllum lanigerum var. austrocoriaceum
Common Name(s): Calanolide A

Medically reviewed by Drugs.com. Last updated on Sep 21, 2023.

Clinical Overview

Use

Calanolide has demonstrated antimicrobial and antiviral activities, with interest focused on applications in HIV; however, clinical trial data are lacking to support use for any indication.

Dosing

Clinical data are lacking to provide dosing recommendations for C. lanigerum or its extracts.

Contraindications

Contraindications have not been identified.

Pregnancy/Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Because calanolide A is a relatively new product, data are limited regarding potential adverse reactions.

Toxicology

No data.

Scientific Family

Botany

The tree C. lanigerum var. austrocoriaceum grows in the rain forest of the Malaysian state of Sarawak on the island of Borneo. There are at least 200 species in the genus Calophyllum.(McKee 1998, Shenon 1994, USDA 2021) The calanolide A component is isolated from the latex.

History

In 1987, an Illinois team of scientists contracted by the National Cancer Institute (NCI) to search for natural drugs in tropical rain forests obtained specimen samples from various rain forest trees, one of which was C. lanigerum. Four years later, the NCI discovered that a preparation from this gum tree was active against HIV-1.(Defant 2015, Nahar 2020, Shenon 1994) In 2016, Craun Research announced that phase 1 trials with calanolide A had been completed. In 2017, F18, a synthetic structural analog of calanolide A, demonstrated more potent anti-HIV activity than calanolide A.(Nahar 2020)

Chemistry

Plants from the genus Calophyllum have been shown to contain xanthones, steroids, triterpenes, coumarins, and benzopyrans. Calanolide A is an 11,12-dihydro-2H,6H,10H-dipyrano[2,3-f:20,30-h]chromen-2-one substituted by a hydroxyl (–OH) group at C-12; methyl groups at positions 6, 6, 10, and 11; and a propyl group at C-4. It is considered a dipyranocoumarin, with nonnucleoside HIV-1–specific reverse transcriptase–inhibiting properties.(McKee 1996, McKee 1998, Nahar 2020) Its molecular formula is C22H26O5.(Nahar 2020) Many studies of the genus Calophyllum include findings regarding structural representations, related compounds and their derivatives, and modifications of the molecule.(Galinis 1996, Kashman 1992, Ma 2008, McKee 1996, McKee 1998, Sekino 2004, Yu 2007, Zembower 1997) Calanolide A has been synthesized in the lab and was found to have similar actions to the natural product.(Flavin 1996) Calanolides are among the first plant-based compounds to show activity against HIV-1.(Nahar 2020)

Uses and Pharmacology

Antimicrobial activity

In vitro data

An in vitro study investigated the activity of modified calanolides against Mycobacterium tuberculosis.(Liu 2015)

Antiviral activity

Early interest persists in using Calophyllum extracts in the management of HIV infections,(Matthée 1999, Newman 1998) particularly for clinically relevant mutant HIV strains.(Usach 2013) Calanolide A and related compounds from the genus Calophyllum have demonstrated antiviral activity, including nonnucleoside reverse transcriptase inhibition(Matthée 1999, Newman 1998) and activity against influenza H3N1 and H1N1 viruses.(Rajasekaran 2013)

Animal and in vitro data

Calanolide A has demonstrated synergistic effects with other anti-HIV drugs in cell and animal models.(Nahar 2020)

Clinical data

Published clinical research on C. lanigerum is lacking. Calanolide A has been investigated in phase 1 clinical trials to evaluate safety, tolerability, and pharmacokinetics.(Creagh 2001, Usach 2013) In 2016, Craun Research announced that phase 1 trials with calanolide A had been completed.(Nahar 2020)

Cancer

Calanolide A is being investigated as an antitumor agent.(Defant 2015, Nahar 2020)

Dosing

Clinical data are lacking to provide dosing recommendations for C. lanigerum or its extracts.

Calanolide A is an investigational anti-HIV drug that has been evaluated in early phase 1 single-dose safety and pharmacokinetic clinical trials in healthy subjects (oral dose range, 200 to 800 mg); however, safety and efficacy remain to be defined, and calanolide A is not available for use.(Creagh 2001, Nahar 2020)

Calanolides are associated with high safety margins and favorable pharmacokinetic profiles; while several analogues of the naturally occurring calanolides have been synthesized, further research is required to commercially bring any of the calanolide candidates, natural or synthetic, to the anti-HIV drug market.(Nahar 2020)

Pregnancy / Lactation

Avoid use. Information regarding safety and efficacy in pregnancy and lactation is lacking.

Interactions

None well documented.

Adverse Reactions

Because calanolide A is a relatively new product, data are limited regarding potential adverse reactions. An early phase 1 single-dose safety and pharmacokinetic clinical trial in healthy subjects demonstrated a favorable safety profile.(Creagh 2001, Usach 2013)

Toxicology

Information is limited. Animal studies demonstrated that oral calanolide A is generally well tolerated in doses of up to 150 mg/kg in rats and 100 mg/kg in dogs. In a study of healthy patients without HIV, there were no serious or toxic effects with calanolide A use.(Nahar 2020)

References

Disclaimer

This information relates to an herbal, vitamin, mineral or other dietary supplement. This product has not been reviewed by the FDA to determine whether it is safe or effective and is not subject to the quality standards and safety information collection standards that are applicable to most prescription drugs. This information should not be used to decide whether or not to take this product. This information does not endorse this product as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this product. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this product. This information is not specific medical advice and does not replace information you receive from your health care provider. You should talk with your health care provider for complete information about the risks and benefits of using this product.

This product may adversely interact with certain health and medical conditions, other prescription and over-the-counter drugs, foods, or other dietary supplements. This product may be unsafe when used before surgery or other medical procedures. It is important to fully inform your doctor about the herbal, vitamins, mineral or any other supplements you are taking before any kind of surgery or medical procedure. With the exception of certain products that are generally recognized as safe in normal quantities, including use of folic acid and prenatal vitamins during pregnancy, this product has not been sufficiently studied to determine whether it is safe to use during pregnancy or nursing or by persons younger than 2 years of age.

More about calanolide a

Related treatment guides

Creagh T, Ruckle JL, Tolbert DT, et al. Safety and pharmacokinetics of single doses of (+)-calanolide a, a novel, naturally occurring nonnucleoside reverse transcriptase inhibitor, in healthy, human immunodeficiency virus-negative human subjects. Antimicrob Agents Chemother. 2001;45(5):1379-1386.11302799
Defant A, Mancini I, Tomazzolli R, Balzarini J. Design, synthesis, and biological evaluation of novel 2H-pyran-2-one derivatives as potential HIV-1 reverse transcriptase inhibitors. Arch Pharm (Weinheim). 2015;348(1):23-33. doi:10.1002/ardp.20140023525523431
Flavin MT, Rizzo JD, Khilevich A, et al. Synthesis, chromatographic resolution, and anti-human immunodeficiency virus activity of (+/-)-calanolide A and its enantiomers. J Med Chem. 1996;39(6):1303-1313.8632437
Galinis DL, Fuller RW, McKee TC, et al. Structure-activity modifications of the HIV-1 inhibitors (+)-calanolide A and (-)-calanolide B. J Med Chem. 1996;39(22):4507-4510.8893846
Genus Calophyllum L. USDA, NRCS. 2021. The PLANTS Database (http://plants.usda.gov, 17 August 2021). National Plant Data Team, Greensboro, NC 27401-4901 USA.
Kashman Y, Gustafson KR, Fuller RW, et al. The calanolides, a novel HIV-inhibitory class of coumarin derivatives from the tropical rainforest tree, Calophyllum lanigerum. J Med Chem. 1992;35(15):2735-2743.1379639
Liu Z, Guo X, Liu G. Modified calanolides incorporated with furan-2-nitro mimics against Mycobacterium tuberculosis. Bioorg Med Chem Lett. 2015;25(6):1297-1300. doi:10.1016/j.bmcl.2015.01.04625681226
Ma T, Liu L, Xue H, et al. Chemical library and structure-activity relationships of 11-demethyl-12-oxo calanolide A analogues as anti-HIV-1 agents. J Med Chem. 2008;51(5):1432-1446.18284187
Matthée G, Wright AD, König GM. HIV reverse transcriptase inhibitors of natural origin. Planta Med. 1999;65(6):493-506.10483367
McKee TC, Covington CD, Fuller RW, et al. Pyranocoumarins from tropical species of the genus Calophyllum: a chemotaxonomic study of extracts in the National Cancer Institute collection. J Nat Prod. 1998;61(10):1252-1256.9784162
McKee TC, Fuller RW, Covington CD, et al. New pyranocoumarins isolated from Calophyllum lanigerum and Calophyllum teysmannii. J Nat Prod. 1996;59(8):754-758.8792623
Nahar L, Talukdar AD, Nath D, et al. Naturally occurring calanolides: occurrence, biosynthesis, and pharmacological properties including therapeutic potential. Molecules. 2020;25(21):4983. doi:10.3390/molecules2521498333126458
Newman RA, Chen W, Madden TL. Pharmaceutical properties of related calanolide compounds with activity against human immunodeficiency virus. J Pharm Sci. 1998;87(9):1077-1080.9724557
Rajasekaran D, Palombo EA, Chia Yeo T, et al. Identification of traditional medicinal plant extracts with novel anti-influenza activity. PLoS One. 2013;8(11):e79293.24312177
Sekino E, Kumamoto T, Tanaka T, Ikeda T, Ishikawa T. Concise synthesis of anti-HIV-1 active (+)-inophyllum B and (+)-calanolide A by application of (-)-quinine-catalyzed intramolecular oxo-Michael addition. J Org Chem. 2004;69(8):2760-2767.15074925
Shenon P. Hunt in forests of Borneo aims to track down natural drugs. New York Times. December 6, 1994. Accessed August 17, 2021. https://www.nytimes.com/1994/12/06/science/hunt-in-forests-of-borneo-aims-to-track-down-natural-drugs.html
Usach I, Melis V, Peris JE. Non-nucleoside reverse transcriptase inhibitors: a review on pharmacokinetics, pharmacodynamics, safety and tolerability. J Int AIDS Soc. 2013;16(1):1-14. doi:10.7448/IAS.16.1.1856724008177
Yu D, Morris-Natschke SL, Lee KH. New developments in natural products-based anti-AIDS research. Med Res Rev. 2007;27(1):108-132.16888749
Zembower DE, Liao S, Flavin MT, et al. Structural analogues of the calanolide anti-HIV agents. Modification of the trans-10,11-dimethyldihydropyran-12-ol ring (ring C). J Med Chem. 1997;40(6):1005-1017.9083491

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